The interaction of the uranyl(VI) ion (UO22+) with DNA and its light-induced cleavage of DNA has been studied using flow-linear dichroism and P-32-endlabeled oligonucleotides. It was found that binding of uranyl ion to DNA is a prerequisite for photocleavage; from run-off experiments the binding constant was estimated to be of the order of 10(10) M-1 at pH 4. The angular orientation of the O=U=O2+ chromophore is consistent with binding by bridging phosphate groups on opposite strands of the minor groove of DNA; at higher DNA concentration aggregation indicates intermolecular bridging as well. The uranyl-mediated photocleavage of DNA is not influenced by the presence of O2, is more efficient at low pH (